Radioactive aliphatic compounds



States. Patent C RADIOACTIVE ALIPHATIC COMPOUNDS Willard F. Libby, Washington, D. C., and Ariel G. Schrodt, Silver Spring, Md, assignors to the United States of America as represented by the Secretary of the Air Force No Drawing. Application April 8, 1955' Serial No. 500,307

Claims. (Cl. 204-154.2)

This invention is a method of producing aliphatic compounds labeled with radioactive carbon-l4 atoms.

It is an object of this invention toprovide a direct and practical method for producing aliphatic compounds labeled with radioactive carbon-14 atoms.

Another object of this invention is to provide an improved method of producing aliphatic radioactivehydrocarbons useful for tracer studies, particularly in the petroleum industry.

It is a further object of this invention to provide an improved method of producing aliphatic radioactive pharmaceutical compounds useful in tracer studies in the pharmaceutical industry.

The above objects and other objects which will be apparent from the following detailed description are accomplished by this invention which is a method of producing aliphatic compounds labeled with radioactive carhon-l4 wherein an intimate mixture of an aliphatic compound and a nitrogen compound is irradiated with thermal neutrons at a high enough neutron flux and for a sufficient time to produce usable quantities of the desired product. An aliphatic compound labeled with radioactive carbon-14 atoms is defined as an aliphatic compound consisting, in part, of molecules having one or more carbon-14 atoms therein. It is preferred to charge a single compound of high purity as the aliphatic component. Likewise the nitrogen compound should be of high purity" to prevent contamination of the irradiated product and obtain the highest yields of the desired product. Purities of the order of 99% or higher are preferred butlower purity materials can be used with the 'result thatlower yields will be obtained and it will be more difficult to work up the reaction products to separate the desired compound or compounds. Normally practical yields of labeled aromatic or heterocyclic compounds will not be obtained by the same irradiation techniques due to the complexity of the reactions involved with these compounds. The aliphatic compounds used as raw materials in this process can be saturated or unsaturated hydrocarbons and substituted hydrocarbons of all kinds including metal esters or soaps, etc. It is preferred to use normally liquid or solid aliphatic compounds in my process since the molecules will be more concentrated and the yields much higher than with gases, unless the gases are under extremely high pressures and substantially as dense as liquids. This'method gives particularly high yields of the desired labeled compound when using saturated aliphatic hydrocarbons, particularly normally liquid aliphatic hydrocarbons boiling below about 600 F. Satisfactory yields will be obtained of the desired labeled compound from liquid aliphatic alcohols but these yields will be appreciably lower than from the hydrocarbons. v

Nitrogen compounds which can be used as a source as nitrogen-14 in the process can be either inorganic or organic nitrogen compounds. The form of the nitrogen is unimportant due to the nature of the reaction involved.

= Patented Oct.'7', 1958 For the highest yields it is important that the'nitrogen compound used beevenly dispersed throughout the aliphatic compound. If a liquid aliphatic compound is being processed normally it is preferred to use a nitrogen compound which is soluble therein since then no problem of intimately dispersing the nitrogen compound in the aliphatic compound is presented. It is preferred that normally liquid or solid nitrogen compounds be used to give a high concentration of nitrogen atoms for irradiation. Gaseous compounds can be used but are not as desirable as the solid and liquid nitrogen compounds except pos sibly where the gaseous nitrogen compound is very soluble in the particular aliphatic compound being processed. Classes of compounds which are particularly desirable as sources of nitrogen in this process are aromatic and aliphatic amines. About 5 mole percent of nitrogen compound in the mixtureof aliphatic compound and nitrogen compound is a satisfactory concentration. This does not necessarily represent an optimum mixture for the highest yield, however, and a higher or lower concentration of the nitrogen compound can be used.

The irradiation is done with thermal neutrons, i. e., neutrons-having energies of about 0.03 ev. Suitable sources of these thermal neutrons are nuclear reactors (piles); cyclotrons and the like; radioactive compounds, such as polonium-beryllium sources, etc. The preferred source of thermal neutrons, however, is the nuclear reactor or pile. This source of neutrons will give a high concentration or flux of thermal neutrons for irradiation which will allow 'the time required in the irradiation step to be substantially reduced as compared to irradiation with a low flux source. A 10 neutrons per cm. per second source is adequate but a higher flux will allow shorter irradiation time while a lower flux will require more irradiation time to obtain a practical yield of the desired labeled compound.

An irradiation mixture can be worked up by a number of dilferent techniques toseparate the desired compound or compounds from the other materials of the reaction mixture. Perhaps the most satisfactory method of working up the reaction mixture is to use a conventional distillation technique wherein carriers are added to facilitate the separation of the minute quantities of radioactive compounds.

Described below are some examples of theuse of the process in'producing aliphatic compounds labeled with carbon-14. In these examples the total yield of mixed labeled molecules is of the order of microgram quantities.

EXAMPLE I A 5 mole percent solution of aniline in normal pentane was made. Both materials were 99+% purity. 20 cc.

of this solution was inclosed in a quartz tube and irradiated for one week in the heavy water (GP-3') pile at the Argonne National Laboratory at a flux of 10 neutrons per cm. per second. Table I shows an analysis of the products of the irradiation step.

EXAMPLE 11 2-0 cos. of a 5 mole percent solution of ethylarnine in normal pentane which was inclosed in a quartz'tube was irradiated for one week in the CP-3 pile at a flux of 10 neutrons per cm. per second. The irradiated mixture was worked up by the usual distillation techniques using carriers, and the results of the analysis of this mixture are shown in Table 1-1.

EXAMPLE III A 4.25 mole percent solution of aniline inv methanol was irradiated in the same manneras the samples of the other examples and the product worked up by the conveni l rat ans mole-percenidnaline. a aaarjaaaaaai g i mana es lHeptan Thc' =anal- I i 'ysis of. the: irradiated product is reported-in :TableIlL. i

- t en 'Iablell insole percent mytamras emsne dare I i imethanol datm 1 l I i an aromatic-amine, aniline. Table l-shows data wherein: i i

the nitrogen source is an aliphatic aminc namely :ethy-lr' amine; =Complete activity data is not shown in Tablell but it is; shown that the activity is highest in the npentane fraction and the. percentage activity is substantially the same. namely 25%, as: whenithe aromatic amine was used as the source of nitrogen; -In other; words :it is indicated z I that the source of znitrogen-isnot critical. I P 5 Table- III shows analysis: data ottheirradia ted sample: from Example TIL; i Aniline was the sourceot. nitrogen I andmethanol the: compound to. be; labeled. The reason; l for the-highest activity being :found in :thegas or methane I fraction is believed to. ibe the resulti of carbon-l4; atoms. I I

= replacing: oxygen; atotns in methanol :to "for-m radioactive ethane: 5 Also other; radioactive gases including. radioaci-f Z tivecarbon oxides probably formed. by other rjeac tions. 50f the other-fractions the I greatest activity is. inv I the methanol: fractionindicating: the productto I substantial and useful amouneotthe desired radioactiv i methanol. The yield. iniradioactivc form. of: thealiphatic alcohol charged; to: the: process would undoubtedly have:

, 1 been appreciably higher had higher: alcoholthan methanoh;

suolras, ethanol; propanol; .butanol, etc, been used due to the nature; of the process. :The amount of activity. foundin the basic: compounds. is shownbut'notincluded 5 in the percentage activity calculations. 3 1 I i Obviously ;many: modifications and variations in. the appended claims 3 j =What-=is {claimed -is; I I

A rnethod- :of i labeling the I i i Table-HIM i25imole percent anatmetn Gmssof 1 Percent wysamnlecfah cl tez Carrier p i. Derive 13PM 'tivo. X Basic I 3 Activity Methane 184 -195 to 4. 8 4. 87 38. 1 65 25 to 72 10. 4 2. 25 17. 6 78 72 to 84 7. 9 1. 19 9. 3 97 84 to 105 8.0 1.30 10. 2 118 105 to 122 8. 1 0. 88 6. 8

130 122 to 150 8. l 0. 70 5. 5 Higher alcohols 184 150 1. 4 1. I 12. 5 Aniline (basic 'cpds) 1. 41

active compounds were removed by acid extraction. Then carriers were added to the substantially base'free residue from the extraction step and this mixture was distilled. The various fractions from the distillation step were analyzed for absolute activity and reported as disintegrations per minute (DPM). The irradiated mixtures of Examples -II and III were worked up in like fashion to that of Example 1. Percent of total non-basic activity was calculated from the information on the individual fractions.

The n-pentane fraction of Table 1 contains 25+% radioactivity and this is almost entirely due to n-pentane labeled with carbon-14. No other fraction carries so much radioactivity. It is indicated that labeling of molecules of the aliphatic hydrocarbon charged to the irradiation stop tendsto be the predominant reaction.

.-In Table -I analysis data was presented in which the nitrogen for conversion to carbon-l4 was furnished by bon labeled with radioactive carbon-l4 from the irradiated mixture.

2. The method of claim 1 wherein the hydrocarbon is an alcohol.

3. A method of labeling aliphatic compounds with radioactive carbon-M atoms comprising irradiating in a nuclear reactoran. intimate mixture of a first compound which is a saturated normally-liquid hydrocarbon and a second compound which is a nitrogen-containing compound, the flux of the radiation source being about 10 neutrons per cm. per second, the mixture containing about 5 mole percent of the second compound in the first compound, and separating the resultant hydrocarbon labeled with radioactive carbon-14 from the irradiated mixture. i

4. The method of claim 3 wherein the hydrocarbon is an alcohol and the nitrogen-containing compound is an amine which is soluble in said alcohol.

5. A method of producing aliphatic compounds labeled with radioactive carbon-l4 atoms comprising irradiating in a nuclear reactor having a flux of about. 10 neutrons per cm. per second an intimate mixture of a major amount of a saturated normally-liquid alcohol and a minor amount of an amine which is soluble in said alcohol, said mixture containing about 5 mole percent of amine in alcohol, and separating the resultant alcohol labeled with radioactive carbon-14 from the irradiated mixture.

6. The method of claim 5 wherein said alcohol is methyl alcohol and said amine is aniline.

7. A method of producing aliphatic compounds labeled with radioactive carbon-l4 atoms comprising irradiating in a nuclear reactor having a flux of about 10 neutrons percm. per second an intimate mixture of a major amount of a normally-liquid hydrocarbon and a a i the. i

invention as hereinbefore setzfiorth may be made without:

. departing trom-thespirit and scope thereof and therefore only such l-irnitationsshould be imposed .as are; indicated 1 I compounds with:

; radioactive carbon 4; atoms comprising irradiating zwith;

I thermal .neutronsanintimate mixture ota firstcompound which; is a saturated normally-liquid hydrocarbon; and a second compound: which :is: a nitrogen containing come i I pound theflux of the radiation source being about 10. 1:

. 5 ne ro ge r an-i; Pe t ewn about 55: moleipercent o'ti the s v first compound, and separatingthe resultant hydrocar :rnixture containing: f 1 d? compound zin elie- References Cited in the file of this patent lflankwich et al.: J. Chem. Phys," vol. 14, pp. 131-140 March 1946.

=KAPL-731, AEC Document by Mincher, dated April 2, 1952 (Declassified Feb. 15, 1955), page 5.

Isotopic Carbon by M. Calvin et 21., John Wiley & Sons, New York (1949), pp. 5-7.

Annular Review of Nuclear Science, vol. I (1952), pub. by Annual Reviews, Inc., Stanford, Califi, pp. 526.

The Science and Engineering of Nuclear Power, vol. H, Clark Goodman Addison, Wesley Press (1949), pp. 223-230. 

1. A METOD OF LABELING ALIPHATIC COMPOUNDS WITH RADIOACTIVE CARBON-14 ATOMS COMPRISING IRRADIATING WITHH THERMAL NEUTRONS AN INTIMATE MIXTURE OF A FIRST COMPOUND WHICH IS A SATURATED NORMALLY-LIQUID HYDROCARBON AND A SECOND COMPOUND WHICH IS A NITROGEN-CONTAINING COMPOUND, THE FLUX OF THE RADIATION SOURCE BEING ABOUT 10**1111 NEUTRONS PER CM.2 PER SECOND, THE MIXTURE CONTAINING ABOUT 5 MOLE PERCENT OF THE SECOND COMPOUND IN THE FIRST COMPOUND, AND SEPARATING THE RESULTANT HYDROCARBON LABELED WITH RADIOACTIVE CARBON-14 FROM THE IRRADIATEDD MIXTURE. 